Abstract
The human p68 kinase is an interferon-regulated enzyme that inhibits protein synthesis when activated by double-stranded RNA. We show here that when expressed in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing phenotype resulting from an inhibition of polypeptide chain initiation consistent with functional protein kinase activity. This slow growth phenotype was reverted in yeast by two different mechanisms: expression of the p68 kinase N-terminus, shown to bind double-stranded RNA in vitro and expression of a mutant form of the α-subunit of yeast initiation factor 2, altered at a single phosphorylatable site. These results provide the first direct in vivo evidence that the p68 kinase interacts with the α-subunit of eukaryotic initiation factor 2. Sequence similarity with a yeast translational regulator, GCN2, further suggests that this enzyme may be a functional homolog in higher eukaryotes, where its normal function is to regulate protein synthesis through initiation factor 2 phosphorylation.
Original language | English |
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Pages (from-to) | 1553-1562 |
Number of pages | 10 |
Journal | The EMBO Journal |
Volume | 11 |
Issue number | 4 |
Publication status | Published - 1 Jan 1992 |
Externally published | Yes |
Keywords
- dsRNA
- eIF-2α phosphorylation
- GCN2
- Growth inhibition
- p68 Kinase